依拉维辛根除铜绿假单胞菌宿存细胞

IF 4 2区 医学 Q2 CHEMISTRY, MEDICINAL
ACS Infectious Diseases Pub Date : 2024-12-13 Epub Date: 2024-11-13 DOI:10.1021/acsinfecdis.4c00349
Sweta Roy, Zeynep S Cakmak, Salma Mahmoud, Mahsa Sadeghzadeh, Guirong Wang, Dacheng Ren
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引用次数: 0

摘要

铜绿假单胞菌是导致顽固性感染的主要细菌病原体。抗生素无法清除此类感染的一个主要原因是存在一种叫做顽固细胞的休眠亚群。要根除顽固细胞,就必须改变药物开发策略,从注重抑制生长的传统策略转向寻找能杀死休眠细胞的新线索。在这项研究中,我们证明了麦拉伐环素能有效地在铜绿假单胞菌的宿主细胞中积累,从而在唤醒过程中强力杀灭宿主细胞,包括野生型菌株及其粘液突变体的浮游培养物和生物膜中的宿主细胞。利用小鼠肺部感染模型进一步在体内验证了依拉维辛对控制宿主细胞的作用。总之,这些结果证明了通过靶向休眠来控制细菌病原体宿主细胞的可能性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Eradication of Pseudomonas aeruginosa Persister Cells by Eravacycline.

Pseudomonas aeruginosa is a leading bacterial pathogen that causes persistent infections. One major reason that antibiotics fail to clear such infections is the presence of a dormant subpopulation called persister cells. To eradicate persister cells, it is important to change drug development from traditional strategies that focus on growth inhibition to the search for new leads that can kill dormant cells. In this study, we demonstrate that eravacycline can effectively accumulate in P. aeruginosa persister cells, leading to strong killing during wakeup, including persister cells in both planktonic cultures and biofilms of the wild-type strain and its mucoid mutant. The effects of eravacycline on persister control were further validated in vivo using a lung infection model in mice. Collectively, these results demonstrate the possibility to control persister cells of bacterial pathogens by targeting dormancy.

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来源期刊
ACS Infectious Diseases
ACS Infectious Diseases CHEMISTRY, MEDICINALINFECTIOUS DISEASES&nb-INFECTIOUS DISEASES
CiteScore
9.70
自引率
3.80%
发文量
213
期刊介绍: ACS Infectious Diseases will be the first journal to highlight chemistry and its role in this multidisciplinary and collaborative research area. The journal will cover a diverse array of topics including, but not limited to: * Discovery and development of new antimicrobial agents — identified through target- or phenotypic-based approaches as well as compounds that induce synergy with antimicrobials. * Characterization and validation of drug target or pathways — use of single target and genome-wide knockdown and knockouts, biochemical studies, structural biology, new technologies to facilitate characterization and prioritization of potential drug targets. * Mechanism of drug resistance — fundamental research that advances our understanding of resistance; strategies to prevent resistance. * Mechanisms of action — use of genetic, metabolomic, and activity- and affinity-based protein profiling to elucidate the mechanism of action of clinical and experimental antimicrobial agents. * Host-pathogen interactions — tools for studying host-pathogen interactions, cellular biochemistry of hosts and pathogens, and molecular interactions of pathogens with host microbiota. * Small molecule vaccine adjuvants for infectious disease. * Viral and bacterial biochemistry and molecular biology.
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